Aarhus University Seal

Inter-α-inhibitor heavy chain H4 and sepsis-related coagulation disturbances: Another link between innate immunity and coagulation

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

BACKGROUND: The protease inhibitor inter-α-inhibitor heavy chain H4 (ITIH4) has been described as an acute-phase reactant and could potentially aid in sepsis monitoring and prognostication.

OBJECTIVES: To investigate ITIH4 plasma levels in sepsis patients compared with healthy controls and to examine the association between ITIH4 and acute-phase response markers, blood coagulation, and organ dysfunction in sepsis.

METHODS: We performed a post hoc study to a prospective cohort study. Patients with septic shock (n = 39) were enrolled upon intensive care unit admission. ITIH4 was analyzed using an in-house immunoassay. Standard coagulation parameters, thrombin generation, fibrin formation and lysis, C-reactive protein, organ dysfunction markers, Sequential Organ Failure Assessment score, and disseminated intravascular coagulation (DIC) score were registered. ITIH4 levels were also investigated in a murine Escherichia coli sepsis model.

RESULTS: ITIH4 did not display acute-phase behavior as mean ITIH4 levels were not increased in patients with septic shock or in E. coli-infected mice. However, ITIH4 exhibited large interindividual variation in patients with septic shock compared with healthy controls. Low ITIH4 was associated with sepsis-related coagulopathy, including a high DIC score (mean ITIH4: DIC, 203 μg/mL vs non-DIC, 267 μg/mL, P = .01), low antithrombin ( r = 0.70, P < .0001) and decreased thrombin generation (mean ITIH4: first peak thrombin tertile, 210 μg/mL vs third peak thrombin tertile, 303 μg/mL, P = .01). ITIH4 showed moderate correlation with arterial blood lactate (ρ = -0.50, P < .001) but only weak correlations with C-reactive protein, alanine transaminase, bilirubin, and Sequential Organ Failure Assessment score (all, ρ < 0.26, P > .05).

CONCLUSION: ITIH4 is associated with sepsis-related coagulopathy but is not an acute-phase reactant during septic shock.

Original languageEnglish
Article number100078
JournalResearch and Practice in Thrombosis and Haemostasis
Publication statusPublished - Feb 2023

Bibliographical note

© 2023 The Authors.

    Research areas

  • Acute-phase reaction, ITIH4 protein, human, disseminated intravascular coagulation, multiple organ failure, prognosis, sepsis

See relations at Aarhus University Citationformats

ID: 312716044